Downloaded from http://jnis.bmj.com/ on March 16, 2015 - Published by group.bmj.com
Editor's column
The road not taken Italo Linfante Two roads diverged in a yellow wood, And sorry I could not travel both And be one traveler, long I stood And looked down one as far as I could To where it bent in the undergrowth… … I shall be telling this with a sigh Somewhere ages and ages hence: Two roads diverged in a wood, and II took the one less traveled by, And that has made all the difference. Robert Lee Frost (San Francisco, March 26, 1874—Boston, January 29, 1963)
In 1991 Guido Guglielmi et al in the first of two manuscripts reported the basic functioning of detachable coils.1 In the second article, the authors demonstrated aneurysmal thrombosis in 70–100% of their 15 patients treated with this new technology.2 On 8 September 1995, the Food and Drug Administration approved commercial sale of the Guglielmi detachable coils (GDC). Unquestionably, GDC started a revolution in neurosurgery by changing forever the way we treat cerebral aneurysms. In 2002, the Lancet published the results of International Subarachnoid Aneurysm Trial (ISAT).3 The absolute risk reduction for dependency or death in the endovascular group was 6.9% and the relative risk reduction was 22.6%. At 1 year, the absolute risk reduction was 7.4%. The early survival advantage of patients treated with endovascular embolization compared with patients treated with microsurgical clipping was maintained for up to 7 years and was significant. The trial was rigorous, scientifically solid, and brilliantly conducted. However, abandoning microsurgical clipping for a much less traveled road, which in this case goes from the femoral artery to the cerebral circulation, was met with skepticism. Among the many, these included Harbaugh, Heros and Hadley who in an editorial to ISAT in 2003 stated: “The results from ISAT might not be applicable to patients in the USA where practice patterns, particularly in reference to the degree of subspecialization of neurovascular surgeons in major centers, are
Correspondence to Dr Italo Linfante, Department of Endovascular Neurosurgery, Interventional Neuroradiology, Herbert Wertheim College of Medicine, Florida International University, Baptist Cardiac and Vascular Institute, 8900 North Kendal Drive, Miami, FL 33176, USA; [email protected]; [email protected]
different.”4 The authors concluded “… to extrapolate the early results of this study to all patients with ruptured aneurysms would be a misinterpretation of the ISAT data and a serious disservice to our patients and our profession”.4 Instead, ISAT proved to be a landmark clinical trial in neurosurgery. The trial withstood the test of time by confirming the superiority of the endovascular approach in comparison with traditional microsurgical clipping. At present, a Medline search on coil embolization of aneurysms yields 2761 articles. Endovascular embolization either with detachable coils or with new devices has steadily increased to treat millions of patients worldwide. Furthermore, the less travelled road of the endovascular approach to treat cerebral aneurysms has created many new roads. The brilliant mathematical analysis of flow dynamics between the aneurysmal sac and the parent artery by Wakhloo and Lieber5 gave birth to flow diverter (FD) technology. This new approach was a paradigm shift focusing on the parent vessel rather than treatment of the aneurysmal sac. Over the past few years, the FD has become invaluable for treating the challenging and ‘untreatable’ aneurysms.6 A FD may soon be a better choice for aneurysms now treated with a standard coil or stent-assisted coil embolisation.5 6 In addition, new devices, new platforms for stents and FDs are being developed. If the endovascular approach has been successful for the treatment of cerebral aneurysms, the road appears to be more challenging for the treatment of acute ischemic stroke. In 1995 the National Institute of Neurological Disorders and Stroke (NINDS) investigators published the result of a randomized controlled trial on IV tissue plasminogen activator (tPA) versus placebo in acute ischemic stroke.7 The NINDS trials followed three wellperformed, but negative, trials.8–10 Undoubtedly, the NINDS IV tPA trial introduced the concept of acute, timedependent therapy in cerebral ischemia. This was a major step forward compared with the traditionally conservative approach to patients with stroke, mostly consisting of supportive care, rehabilitation, and secondary stroke prevention. Endovascular recanalization therapy is the most logical development on the road to treat acute ischemic stroke successfully.
Linfante I. J NeuroIntervent Surg November 2014 Vol 6 No 9
However, three clinical trials— SYNTHESIS Expansion, IMS (Interventional Management of Stroke) III, and MR RESCUE (Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy)—showed that the endovascular approach was no better than standard IV tPA therapy.11–14 It is beyond the scope of this brief editorial to comprehensively analyze the drawbacks of these trials as they have already been extensively discussed in the literature. However, several authors have pointed out that these three trials were performed while recanalization device technology was improving. The SWIFT (Solitaire With Intention For Thrombectomy) and TREVO (Thrombectomy REvascularization of large Vessel Occlusions in acute ischemic stroke) 2 trials showed that current devices for acute stroke intervention can provide faster and higher recanalization rates than previous revascularization technology.14 15 Several clinical trials are now underway. Nevertheless, a major challenge to endovascular intervention for acute stroke is the dramatic time sensitivity of the cerebral tissue to ischemia.16 Time to reperfusion plays a major role in obtaining good outcomes even in the presence of successful recanalization. Recently, Shi et al17 reported predictive factors of poor outcomes despite recanalization in pooled data from the MERCI (Mechanical Embolus Removal in Cerebral Ischemia), TREVO, and TREVO 2 trials. The authors reported an 11% increase in the odds of functional dependence (modified Rankin score (mRS) ≥3) for every 30 min delay from symptom onset to endovascular intervention. In an analysis of the North American Solitaire Stent Retriever Acute Stroke (NASA) registry, we found that total time to recanalization had a 9% increased risk of a poor outcome (mRS ≥3) for every 30 min delay in endovascular intervention.18 In addition, recently, several authors reported more evidence that ischemic core imaging and collateral circulation assessment may correlate with outcomes after thrombectomy and will play a major role in the selection of patients for acute stroke intervention.19–21 In conclusion, despite the enormous progress made over the past decade in the treatment of cerebrovascular diseases, there are many challenges ahead. The scope of this brief editorial was to thank and acknowledge the innovators, the forward thinkers, those who see what everyone else sees but think what nobody else has thought, those who have ‘taken the road less travelled by’. The field of neurointerventional surgery has been built 643
Downloaded from http://jnis.bmj.com/ on March 16, 2015 - Published by group.bmj.com
Editor's column on this premise. Hopefully, despite the challenges ahead the field will continue to evolve by a commitment to innovation. Our patients need it.
4 5
Competing interests None. Provenance and peer review Commissioned; internally peer reviewed.
6
7
To cite Linfante I. J NeuroIntervent Surg 2014;6:643– 644.
8
Accepted 27 August 2014 Published Online First 5 September 2014 J NeuroIntervent Surg 2014;6:643–644. doi:10.1136/neurintsurg-2014-011441
9
10
REFERENCES 1
2
3
644
Guglielmi GI, Viñuela F, Sepetka I, et al. Electrothrombosis of saccular aneurysms via endovascular approach. J Neurosurg 1991;75:1–7. Guglielmi G, Viñuela F, Dion J, et al. Electrothrombosis of saccular aneurysms via endovascular approach. Part 2: Preliminary clinical experience. J Neurosurg 1991;75:8–14. Molyneux A, Kerr R, Stratton I, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients
11
12
13
with ruptured intracranial aneurysms: a randomised trial. Lancet 2002;360:1267–74. Harbaugh RE, Heros RC, Hadley MN. More on ISET. Lancet 2003;361:783–4. Wakhloo AK, Gounis MJ. Revolution in aneurysm treatment: flow diversion to cure aneurysms: a paradigm shift. Neurosurgery 2014;61:111–20. Becske T, Kallmes DF, Saatci I, et al. Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial. Radiology 2013;26:858–68. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–7. Hacke W, Kaste M, Fieschi C, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke: the European Cooperative Acute Stroke Study (ECASS). JAMA 1995;274:1017–25. Hommel M, Boissel JP, Cornu C, et al. Termination of trial of streptokinase in severe acute ischaemic stroke. Lancet 1995;345:57. Donnan GA, Hommel M, Davis SM, et al. Streptokinase in acute ischaemic stroke. Lancet 1995;346:56. Ciccone A, Valvassori L, Nichelatti M, et al. Endovascular treatment for acute ischemic stroke. New Engl J Med 2013;368:904–13. Broderick JP, Palesch YY, Demchuk AM`, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. New Engl J Med 2013;368: 893–903. Kidwell CS, Jahan R, Gornbein J, et al. A trial of imaging selection and endovascular treatment
14
15
16 17
18
19
20
21
for ischemic stroke. N Engl J Med 2013;368: 914–23. Saver JL, Jahan R, Levy EI, et al.; SWIFT Trialists. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet 2012;380:1241–9. Nogueira RG, Lutsep HL, Gupta R, et al.; TREVO 2 Trialists. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet 2012;380:1231–40. Saver JL. Time is brain--quantified. Stroke 2006;37:263–6. Shi ZS, Liebeskind DS, Xiang B, et al. Predictors of functional dependence despite successful revascularization in large-vessel occlusion strokes. Stroke 2014;45:1977–84. Linfante I, Dabus G, Starosciak A, et al. Predictors of poor outcomes despite successful recanalization in patients with acute ischemic stroke. J Neurointerv Surg 2014;6(Suppl 1):A17–18. Yoo AJ, Chaudhry ZA, Nogueira RG, et al. Infarct volume is a pivotal biomarker after intra-arterial stroke therapy. Stroke 2012;43:1323–30. Ribo M, Flores A, Mansilla E, et al. Age-adjusted infarct volume threshold for good outcome after endovascular treatment. J Neurointerv Surg 2014;6:418–22. Liebeskind DS, Jahan R, Nogueira RG, et al.; SWIFT Investigators. Impact of collaterals on successful revascularization in Solitaire FR with the intention for thrombectomy. Stroke 2014;45:2036–40.
Linfante I. J NeuroIntervent Surg November 2014 Vol 6 No 9
Downloaded from http://jnis.bmj.com/ on March 16, 2015 - Published by group.bmj.com
The road not taken Italo Linfante J NeuroIntervent Surg 2014 6: 643-644
doi: 10.1136/neurintsurg-2014-011441 Updated information and services can be found at: http://jnis.bmj.com/content/6/9/643
These include:
References Email alerting service
This article cites 21 articles, 6 of which you can access for free at: http://jnis.bmj.com/content/6/9/643#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
Editor's column
The road not taken Italo Linfante Two roads diverged in a yellow wood, And sorry I could not travel both And be one traveler, long I stood And looked down one as far as I could To where it bent in the undergrowth… … I shall be telling this with a sigh Somewhere ages and ages hence: Two roads diverged in a wood, and II took the one less traveled by, And that has made all the difference. Robert Lee Frost (San Francisco, March 26, 1874—Boston, January 29, 1963)
In 1991 Guido Guglielmi et al in the first of two manuscripts reported the basic functioning of detachable coils.1 In the second article, the authors demonstrated aneurysmal thrombosis in 70–100% of their 15 patients treated with this new technology.2 On 8 September 1995, the Food and Drug Administration approved commercial sale of the Guglielmi detachable coils (GDC). Unquestionably, GDC started a revolution in neurosurgery by changing forever the way we treat cerebral aneurysms. In 2002, the Lancet published the results of International Subarachnoid Aneurysm Trial (ISAT).3 The absolute risk reduction for dependency or death in the endovascular group was 6.9% and the relative risk reduction was 22.6%. At 1 year, the absolute risk reduction was 7.4%. The early survival advantage of patients treated with endovascular embolization compared with patients treated with microsurgical clipping was maintained for up to 7 years and was significant. The trial was rigorous, scientifically solid, and brilliantly conducted. However, abandoning microsurgical clipping for a much less traveled road, which in this case goes from the femoral artery to the cerebral circulation, was met with skepticism. Among the many, these included Harbaugh, Heros and Hadley who in an editorial to ISAT in 2003 stated: “The results from ISAT might not be applicable to patients in the USA where practice patterns, particularly in reference to the degree of subspecialization of neurovascular surgeons in major centers, are
Correspondence to Dr Italo Linfante, Department of Endovascular Neurosurgery, Interventional Neuroradiology, Herbert Wertheim College of Medicine, Florida International University, Baptist Cardiac and Vascular Institute, 8900 North Kendal Drive, Miami, FL 33176, USA; [email protected]; [email protected]
different.”4 The authors concluded “… to extrapolate the early results of this study to all patients with ruptured aneurysms would be a misinterpretation of the ISAT data and a serious disservice to our patients and our profession”.4 Instead, ISAT proved to be a landmark clinical trial in neurosurgery. The trial withstood the test of time by confirming the superiority of the endovascular approach in comparison with traditional microsurgical clipping. At present, a Medline search on coil embolization of aneurysms yields 2761 articles. Endovascular embolization either with detachable coils or with new devices has steadily increased to treat millions of patients worldwide. Furthermore, the less travelled road of the endovascular approach to treat cerebral aneurysms has created many new roads. The brilliant mathematical analysis of flow dynamics between the aneurysmal sac and the parent artery by Wakhloo and Lieber5 gave birth to flow diverter (FD) technology. This new approach was a paradigm shift focusing on the parent vessel rather than treatment of the aneurysmal sac. Over the past few years, the FD has become invaluable for treating the challenging and ‘untreatable’ aneurysms.6 A FD may soon be a better choice for aneurysms now treated with a standard coil or stent-assisted coil embolisation.5 6 In addition, new devices, new platforms for stents and FDs are being developed. If the endovascular approach has been successful for the treatment of cerebral aneurysms, the road appears to be more challenging for the treatment of acute ischemic stroke. In 1995 the National Institute of Neurological Disorders and Stroke (NINDS) investigators published the result of a randomized controlled trial on IV tissue plasminogen activator (tPA) versus placebo in acute ischemic stroke.7 The NINDS trials followed three wellperformed, but negative, trials.8–10 Undoubtedly, the NINDS IV tPA trial introduced the concept of acute, timedependent therapy in cerebral ischemia. This was a major step forward compared with the traditionally conservative approach to patients with stroke, mostly consisting of supportive care, rehabilitation, and secondary stroke prevention. Endovascular recanalization therapy is the most logical development on the road to treat acute ischemic stroke successfully.
Linfante I. J NeuroIntervent Surg November 2014 Vol 6 No 9
However, three clinical trials— SYNTHESIS Expansion, IMS (Interventional Management of Stroke) III, and MR RESCUE (Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy)—showed that the endovascular approach was no better than standard IV tPA therapy.11–14 It is beyond the scope of this brief editorial to comprehensively analyze the drawbacks of these trials as they have already been extensively discussed in the literature. However, several authors have pointed out that these three trials were performed while recanalization device technology was improving. The SWIFT (Solitaire With Intention For Thrombectomy) and TREVO (Thrombectomy REvascularization of large Vessel Occlusions in acute ischemic stroke) 2 trials showed that current devices for acute stroke intervention can provide faster and higher recanalization rates than previous revascularization technology.14 15 Several clinical trials are now underway. Nevertheless, a major challenge to endovascular intervention for acute stroke is the dramatic time sensitivity of the cerebral tissue to ischemia.16 Time to reperfusion plays a major role in obtaining good outcomes even in the presence of successful recanalization. Recently, Shi et al17 reported predictive factors of poor outcomes despite recanalization in pooled data from the MERCI (Mechanical Embolus Removal in Cerebral Ischemia), TREVO, and TREVO 2 trials. The authors reported an 11% increase in the odds of functional dependence (modified Rankin score (mRS) ≥3) for every 30 min delay from symptom onset to endovascular intervention. In an analysis of the North American Solitaire Stent Retriever Acute Stroke (NASA) registry, we found that total time to recanalization had a 9% increased risk of a poor outcome (mRS ≥3) for every 30 min delay in endovascular intervention.18 In addition, recently, several authors reported more evidence that ischemic core imaging and collateral circulation assessment may correlate with outcomes after thrombectomy and will play a major role in the selection of patients for acute stroke intervention.19–21 In conclusion, despite the enormous progress made over the past decade in the treatment of cerebrovascular diseases, there are many challenges ahead. The scope of this brief editorial was to thank and acknowledge the innovators, the forward thinkers, those who see what everyone else sees but think what nobody else has thought, those who have ‘taken the road less travelled by’. The field of neurointerventional surgery has been built 643
Downloaded from http://jnis.bmj.com/ on March 16, 2015 - Published by group.bmj.com
Editor's column on this premise. Hopefully, despite the challenges ahead the field will continue to evolve by a commitment to innovation. Our patients need it.
4 5
Competing interests None. Provenance and peer review Commissioned; internally peer reviewed.
6
7
To cite Linfante I. J NeuroIntervent Surg 2014;6:643– 644.
8
Accepted 27 August 2014 Published Online First 5 September 2014 J NeuroIntervent Surg 2014;6:643–644. doi:10.1136/neurintsurg-2014-011441
9
10
REFERENCES 1
2
3
644
Guglielmi GI, Viñuela F, Sepetka I, et al. Electrothrombosis of saccular aneurysms via endovascular approach. J Neurosurg 1991;75:1–7. Guglielmi G, Viñuela F, Dion J, et al. Electrothrombosis of saccular aneurysms via endovascular approach. Part 2: Preliminary clinical experience. J Neurosurg 1991;75:8–14. Molyneux A, Kerr R, Stratton I, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients
11
12
13
with ruptured intracranial aneurysms: a randomised trial. Lancet 2002;360:1267–74. Harbaugh RE, Heros RC, Hadley MN. More on ISET. Lancet 2003;361:783–4. Wakhloo AK, Gounis MJ. Revolution in aneurysm treatment: flow diversion to cure aneurysms: a paradigm shift. Neurosurgery 2014;61:111–20. Becske T, Kallmes DF, Saatci I, et al. Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial. Radiology 2013;26:858–68. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–7. Hacke W, Kaste M, Fieschi C, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke: the European Cooperative Acute Stroke Study (ECASS). JAMA 1995;274:1017–25. Hommel M, Boissel JP, Cornu C, et al. Termination of trial of streptokinase in severe acute ischaemic stroke. Lancet 1995;345:57. Donnan GA, Hommel M, Davis SM, et al. Streptokinase in acute ischaemic stroke. Lancet 1995;346:56. Ciccone A, Valvassori L, Nichelatti M, et al. Endovascular treatment for acute ischemic stroke. New Engl J Med 2013;368:904–13. Broderick JP, Palesch YY, Demchuk AM`, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. New Engl J Med 2013;368: 893–903. Kidwell CS, Jahan R, Gornbein J, et al. A trial of imaging selection and endovascular treatment
14
15
16 17
18
19
20
21
for ischemic stroke. N Engl J Med 2013;368: 914–23. Saver JL, Jahan R, Levy EI, et al.; SWIFT Trialists. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet 2012;380:1241–9. Nogueira RG, Lutsep HL, Gupta R, et al.; TREVO 2 Trialists. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet 2012;380:1231–40. Saver JL. Time is brain--quantified. Stroke 2006;37:263–6. Shi ZS, Liebeskind DS, Xiang B, et al. Predictors of functional dependence despite successful revascularization in large-vessel occlusion strokes. Stroke 2014;45:1977–84. Linfante I, Dabus G, Starosciak A, et al. Predictors of poor outcomes despite successful recanalization in patients with acute ischemic stroke. J Neurointerv Surg 2014;6(Suppl 1):A17–18. Yoo AJ, Chaudhry ZA, Nogueira RG, et al. Infarct volume is a pivotal biomarker after intra-arterial stroke therapy. Stroke 2012;43:1323–30. Ribo M, Flores A, Mansilla E, et al. Age-adjusted infarct volume threshold for good outcome after endovascular treatment. J Neurointerv Surg 2014;6:418–22. Liebeskind DS, Jahan R, Nogueira RG, et al.; SWIFT Investigators. Impact of collaterals on successful revascularization in Solitaire FR with the intention for thrombectomy. Stroke 2014;45:2036–40.
Linfante I. J NeuroIntervent Surg November 2014 Vol 6 No 9
Downloaded from http://jnis.bmj.com/ on March 16, 2015 - Published by group.bmj.com
The road not taken Italo Linfante J NeuroIntervent Surg 2014 6: 643-644
doi: 10.1136/neurintsurg-2014-011441 Updated information and services can be found at: http://jnis.bmj.com/content/6/9/643
These include:
References Email alerting service
This article cites 21 articles, 6 of which you can access for free at: http://jnis.bmj.com/content/6/9/643#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
